Effects of phytoestrogens on GnRH-induced luteinizing hormone secretion in ovariectomized rats

Ovariectomized rats were pretreated with intravenous estradiol-17 beta (E2), coumestrol or genistein and were challenged 2 h later with GnRH (50 ng/kg BW, i.v.). Blood samples, drawn at the time of GnRH administration and 15 min afterwards, were assayed for luteinizing hormone (LH). While low-dose E2 pretreatment (10 ng/kg BW) significantly enhanced GnRH-induced LH release, high dose E2 pretreatment (1000 ng/kg BW) blocked the GnRH-induced rise. Intermediate-dose E2 pretreatment (100 ng/kg BW) yielded a GnRH response that did not differ from that in the vehicle pretreatment group. At all doses studied, coumestrol pretreatment (10 ng/kg BW, 100 ng/kg BW, and 1000 ng/kg BW) appeared to diminish but not abrogate GnRH-induced LH release. While intermediate-dose genistein pretreatment (100 ng/kg BW) significantly enhanced GnRH-induced LH release, high-dose genistein pretreatment (1000 ng/kg BW) yielded a GnRH response that did not differ from that in the vehicle pretreatment group. Both low-dose (10 ng/kg BW) and very high-dose (10,000 ng/kg BW) genistein pretreatment appeared to inhibit GnRH-induced LH release. The results demonstrate that acute exposure to phytoestrogens alters GnRH-induced LH release in ovariectomized rats. The dose-response pattern of enhanced GnRH-induced LH release at lower pretreatment doses but inhibited GnRH-induced LH release at higher pretreatment doses was observed for E2 and genistein. The potency of genistein appears to be approximately 1/10 that of E2 in this system. Phytoestrogens acutely perturb reproductive neuroendocrine function.